DESCRIPTION (from application): The Mentored Research Scientist Development Award would allow Dr. Sara G. Carlson, PhD, to make a successful transition into conducting independent research in the field of cardiovascular aging. Since Dr. Carlson has a solid foundation in scientific training, it is reasonable to project that toward the end of the mentored research term, she will have developed a significant body of age-related data that will form a basis for independent research status and funding. The objectives of this application are to enable Dr. Carlson to steer her current efforts toward aging research: the research career development plan consists of Dr. Carlson assuming the primary role in conducting this research project, taking course work in scientific integrity, participating in seminars, journal clubs, workshops, and scientific meetings; reading and discussing original research articles in oxidative damage and atherosclerosis; and meeting with mentors and consultants trained in aging, cardiovascular disease, and apoptosis research. The aims of the research are: 1) to identify specific steps in oxysterol- induced apoptotic pathways that are modulated by altered ROS generation and antioxidants in cultured vascular cells, and 2) to characterize age-associated atherosclerotic lesion development in the senescence-accelerated mouse (SAM) model, and explore the extent to which antioxidant supplementation reduces apoptosis during age-associated atherosclerotic lesion formation. These studies will allow the candidate to test the overall hypothesis that antioxidants exert protective effects in the atherosclerotic processes accompanying aging through inhibition of ROS-mediated apoptosis.